Vascular dysfunction in the offspring of AT1 receptor antibody-positive pregnant rats during high-salt diet / 生理学报

ABSTRACT

Antibody against the angiotensin AT1 receptor (AT1-Ab) could disturb placental development. The placenta is the key organ between mother and fetus. Placental damage will seriously impair fetal growth and development in utero, leading to intrauterine growth restriction (IUGR). Based on the fetal origins of adult disease (FOAD) hypothesis, IUGR could increase a propensity to develop adult onset cardiovascular disease (CVD). The present study was designed to determine whether vascular function has changed in the adult offspring of AT1-Ab positive pregnant rats. Twenty four female rats (8-week-old, AT1-Ab negative) were randomly divided into two groups, immunized and vehicle groups. Immunized group received active immunization to establish AT1-Ab-positive model, while vehicle group was subjected to Freund's adjuvant without antigen. After 8 weeks of immunization, the antibody titers in sera from the female rats were detected by enzyme-linked immunosorbent assay (ELISA). Then all the female rats were mated with normal Wistar male rats and became pregnant. Immunized/vehicle group offspring rats (I offspring/V offspring) were raised to 40-week-old under standard chow feeding. Then the two groups' offspring rats were given a high-salt diet for 12 weeks (4% NaCl in chow feeding). Systolic blood pressure (SBP) was measured dynamically by noninvasive blood pressure system. The vascular ring experiment was performed to detect vascular function and reactivity. As detected by ELISA, the titers of antibody peaked at the 8th week (OD values 2.75 ± 0.08 vs 0.33 ± 0.01, P < 0.01 vs vehicle group at the same time point). There was no significant difference of SBP between the two groups' offspring rats during the high-salt diet (P > 0.05). Isolated thoracic aortic rings of I offspring had significantly decreased constriction under norepinephrine treatment (P < 0.01 vs V offspring) and significantly decreased dilation under acetylcholine treatment (P < 0.05 vs V offspring). These results suggest that the offspring of AT1-Ab-positive pregnant rats are more susceptible to vascular functional abnormality while being fed high-salt diet.